Texas lab unlocks keys to alcohol withdrawal headache

About 283 million people worldwide suffer from alcohol use disorder, a debilitating health challenge for which limited therapeutic options are available. The cost to society is estimated at greater than $2 trillion annually. Yu Shin Kim, Ph.D., a neuroscience researcher at The University of Texas Health Science Center at San Antonio states that “Headache is one of the severe withdrawal symptoms that pushes the rehabilitating patient back to alcohol, because people know that, after drinking, alcohol will actually reduce the headache. It becomes a vicious cycle. This is how they develop alcohol dependence.”
Kim, associate professor of oral and maxillofacial surgery in the health science center’s School of Dentistry, and colleagues found that a stress hormone called corticotropin-releasing factor (CRF) activates immune cells known as mast cells in the dura—the thin, transparent membrane under the skull. Dura matter includes peripheral nerve fibers and peripheral blood vessels. CRF plays a pivotal role in activating pain signals during alcohol withdrawal by binding to a specific mast cell receptor, MrgprB2.
“After alcohol withdrawal, the CRF stress hormone is released from the hypothalamus, a brain region that controls many functions,” Kim said. “The CRF travels through peripheral blood vessels to dura matter, where it is released from the vessels and binds to MrgprB2. This signals the mast cells to degranulate, or open, and secrete chemical messengers that induce functions including blood vessel dilation (widening).
“This also activates peripheral nerve fibers extending from trigeminal ganglia neurons, which are sensory neurons. That is how these neurons are sensitized and a person has alcohol-withdrawal headache.”
This research may benefit further studies of various substance use disorder mechanisms including withdrawal, he said. Targeting the interaction between CRF and MrgprB2 could lead to new therapeutic strategies for alleviating pain during alcohol withdrawal and could pave the way for targeted drug therapies, potentially breaking the vicious cycle of addiction.
Source: Mast cell-specific receptor mediates alcohol withdrawal-associated headache in male mice, Neuron (2023). doi.org/10.1016/j.neuron.2023.09.039.